Paratuberculosis, or Johne's disease, in ruminants is a chronic infection of the gastrointestinal tract. Mycobacterium paratuberculosis (MpT) is known to be the causative agent of Johne's disease. Most animals that contract Johne's disease become infected shortly after birth and do not become clinically ill until they are adults. Infection is permanent, there are no viable treatments, and, if not culled, most clinically sick animals eventually die of wasting.
Current estimates indicate that 3.4% of dairy cows in 21.6% of herds and 0.9% of beef cattle in 7.9% of herds in the United States are infected with MpT. Similar data are reported in essentially all other countries. These results demonstrate that Johne's disease is a very serious worldwide problem. Indeed, it has been estimated to have a $0.2-1.5 billion dollar economic impact in the United States due to loss of milk income, increased culling, low culling weights, extended calving intervals, and the unmarketability of breeding stock. Similarly, large economic losses from Johne's disease are also suffered in the sheep industry.
It is generally accepted that for clinical manifestation of paratuberculosis to occur, infection with MpT must occur at a young age. To date, no effective treatment has been reported for infected animals. Moreover, no prophylaxis has been reported that prevents infection. Biosecurity and other management practices have been proposed as a means to control the spread of Johne's disease. It is agreed that the spread of MpT could be lessened by: a) persistent attention to detail; b) avoidance of contact with fecal material from infected animals; and c) culling all infected and all offspring born to infected cattle. However, from a practical perspective, it has been suggested that management alone will likely fail to control infections. Thus, there is a need for viable methods to prevent and control paratuberculosis.
Mycobacteria are major pathogens of humans, as well as animals. There are approximately ten million cases of tuberculosis worldwide with an annual mortality of three million. Leprosy, caused by Mycobacterium leprae, afflicts over ten million people, primarily in developing countries. Mycobacterium tuberculosis and mycobacteria of the Mycobacterium avium-intracellulare group are major opportunistic pathogens of immuno-compromised patients such as AIDS patients. Crohn's disease and Sarcoidosis are postulated to be a result of MpT infection. Most treatments for these diseases require intense and lengthy combinational drug therapy. Such treatments not only allow resistant strains to arise, but for Crohn's patients lasting resolution of disease has yet to be established. Thus, there is a need for more effective treatments for mycobacterial-incited diseases of humans.
Crohn's disease is a chronic, debilitating and potentially fatal disease that bears extensive clinical, pathologic, and systemic similarity to Johne's disease. In the United States, the number of newly diagnosed Crohn's patients is estimated to be 20,000 each year. Crohn's disease is a granulomatous ileo-colitis of unknown etiology. Postulates on the immunopathogenesis of Crohn's disease are that the disease results from an antigenic challenge to the gut-associated lymphoid tissues (GALT). Once triggered, cytokines and other inflammatory mediators released result in chronic and persistent inflammation. This inflammatory reaction is postulated to be the result of hyper-responsiveness of GALT to antigens present within intestinal cells. This hyper-reactivity may be a result of an immunoregulatory defect or from a persistent stimulus, such as MpT antigens. Recent evidence defining a genetic predisposition is consistent with this theory. Thus, there is a need for treatments for Crohn's disease that target MpT in particular.
Animals afflicted with Johne's disease may be the source of MpT that underlie Crohn's disease in humans. For example, MpT may be transmitted to humans through contaminated meat and/or pasteurized milk. MpT is an intracellular pathogen that colonizes and multiplies in phagocytic cells present in blood and other tissues. Since phagocytes are natural constituents of milk, it is not surprising that MpT is found in milk of infected cows. Moreover, MpT is partially resistant to pasteurization presently used commercially. Furthermore, animals that are heavily infected with MpT are usually culled and likely used in the production of ground beef. Inadequate cooking would again result in live MpT being present in food. Thus, any effective treatment of paratuberculosis is likely to reduce the transmission of MpT to humans, which could in turn result in a lower incidence of Crohn's disease.